The purpose of this study was to compare the parenting stress experienced by parents of 121 children from 5 to 9 years old with autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), comorbid ASD+ADHD, and typical development in different domains related to child and parent characteristics using the Parenting Stress Index. The three clinical groups presented greater perceived parenting stress than did the comparison group (CG). The ADHD group obtained higher levels of parenting stress related to attachment and depression than did the other groups. The ASD+ADHD group presented a unique profile of differences from the CG on Health and Spouse subscales. Results highlight the importance in clinical practice of considering parenting stress as a relevant variable for intervention in these clinical families.